A. Field of the Invention
This invention relates to a method of treating hoof thrush in horses and the analogous disease of hoof rot in sheep and cattle. Hoof thrush is a disease of the hoof and frog tissue in horses caused by a variety of pathogens, primarily Spherophorus necrophorus, an anaerobic bacterium. Hoof rot is the analogous hoof disease in sheep, goats and cattle also primarily caused by Spherophorus necrophorus. Merck Veterinary Manual, 6th Edition, Fraser, C. M., Ed. (1986) at pp. 983-84; Ensminger, M. E., The stockman's Handbook, 1st Ed., The Interstate Printers and Publishers (1955) at p.378-79; The Sheepman's Production Handbook, Scott, G. E., Ed., Abegg Printing (1970) at pp. 104-105. Most manure and dirt contains this bacterium and if allowed to pack into the foot and remain for very long, it will attack the hoof. Regular cleaning of the hoof prevents thrush from getting started by allowing air to reach the exposed area. Butler, D., Principles and Practice of Horseshoeing, Butler Publishing, (1974) at p. 176.
Thrush is common in horses and poses a constant problem for owners and grooms. Horses that are particularly susceptible are those that are confined for most of their day and not exercised to a reasonable degree. The predisposing causes of thrush are thus unhygienic conditions, dirty uncleaned feet and lack of frog pressure resulting from poor shoeing or poor foot trimming. Adams, O.R., Lameness in Horses, 2nd Ed., Lea & Febiger (1966) at p. 354. The diagnostic signs of thrush disease (and similarly of hoof rot disease) include: (1) a strong, unpleasant odor and an increased amount of moisture associated with the hoof and frog tissue; (2) a black discharge from the sulcae of the frog tissue; (3) a softening and destruction of the frog tissue (a "cheesy" appearance of the frog); and (4) lameness. Diagnosis of hoof thrush in horses is based primarily on the odor and physical characteristics of the black discharge in the sulci of the frog.
If thrush is not diagnosed and steps taken to treat it, extensive damage to the horse's foot may occur. In severe cases, the thrush infection may penetrate the horny tissues and involve the sensitive structure of the foot. In such cases, the prognosis is poor. The horse may be lame and the foot may show the same signs of infection that would be encountered in puncture wound of the foot. Adams, O.R., supra at p. 355. Similarly with hoof rot, the hoof rot infection may penetrate the horny tissues and the sheep, goat or cow infected may be lame, joint cavities may be involved, and the animal may show fever and depression, lose weight, and even die. The Stockman's Handbook, supra, at p. 378.
It is estimated that hoof thrush affects 5,000,000 horses in the United States alone, and is a constant and significant health problem of horses. It is therefore of great practical importance to be able to provide a method of treating hoof thrush in horses that is fast, simple, effective and humane and which affects a complete cure. It is also of great practical importance to be able to provide a similarly fast, simple and effective method of treating hoof rot in sheep, goats and cattle. Hoof rot is an economically costly disease for commercial raisers of sheep, goats or cattle. Although hoof rot seldom causes death, infected animals generally lose weight and, if lactating, produce less milk. The Stockman's Handbook, supra, at p. 379. The disease, therefore, has an adverse economic impact on the costs of meat and milk production. Hoof rot is a highly contagious disease and in sheep, for example, severe outbreaks of hoof rot may affect up to 75% of a flock at one time. Although, as stated above, the mortality rate from hoof rot is low, loss of condition of adult sheep and nursing lambs plus increased labor, equipment and materials to treat the disease make it one of the most costly sheep diseases. The Sheepman's Production Handbook, supra, at p. 104.
The present invention is a method which is unexpectedly fast and effective for treating hoof thrush in horses using metronidazole. In mild cases of hoof thrush disease, treatment with metronidazole affected a cure within 24 hours. In the most severe and stubborn cases, treatment with metronidazole affected a cure in less than 21 days. The method should be equally effective in the treatment of the analogous disease of hoof rot in sheep, goats and cattle.
B. Description of the Prior Art
1. Metronidazole
As disclosed in the Physicians Desk Reference, 41st Edition, 1987 (hereinafter, the "PDR"), metronidazole (1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole) is a synthetic antiprotozoal and antibacterial agent well-known for its use as a therapeutic agent in humans. It is marketed as a human pharmaceutical in the United States generically as Metronidazole (Elkins-Sinn, Barr, Danbury, Lederle, Zenith), and also under the following trade names: Flagyl.RTM. (Searle), Metric 21.RTM. (Fielding), Metryl.RTM. (Lemmon), Protostat.RTM. (Ortho Pharmaceutical) and Satric.RTM. (Savage).
As disclosed in the PDR, metronidazole is particularly well-known as an antiprotozoal therapeutic agent in humans for the treatment of trichomoniasis and amebiasis. In addition, metronidazole has been found to be active in vitro against certain obligate anaerobic bacteria but has not been found to possess clinically relevant activity against facultative anaerobic bacteria or obligate aerobic bacteria. Specifically, metronidazole has been found to have in vitro and clinical activity against the following human pathogenic bacteria:
(a) anaerobic gram-negative bacilli, including Bacteroides species and Fusobacterium species; PA0 (b) anaerobic gram-positive bacilli, including Clostridium species and susceptible strains of Eubacterium; and PA0 (c) anaerobic gram-positive cocci, including Peptococcus species and Peptostreptococcus species. PA0 1. Removing the cause of the disease by cleanliness and general improvement in the horse's environment; PA0 2. Returning the hoof and frog of the horse to healthy condition through generally accepted husbandry techniques including: (a) removal of necrotic frog tissue, (b) increased exercise and (d) regular and proper trimming of the foot; PA0 3. Applying one or more of the following compounds or products: PA0 1. Removing the cause of the disease by cleanliness and dryness in the animal's environment; PA0 2. Removing the diseased tissue by trimming away the affected part of the hoof according to generally accepted techniques; PA0 3. Applying one or more of the following compounds or products:
Thus, metronidazole has been used to treat anaerobic bacterial infections in humans including: intra-abdominal infection, skin and skin structure infections, gynecologic infections, bacterial septicemia, bone and joint infections, central nervous system infections, lower respiratory tract infections and endocarditis.
The PDR discloses that the treatment of humans with metronidazole is principally by oral administration of metronidazole in table form. For serious infections or in conjunction with certain surgical procedures, metronidazole has been administered intravenously in humans. The PDR does not disclose any topical use of metronidazole.
2. Thrush
Common techniques for treating hoof thrush in horses fall into three overlapping areas:
a. formalin; PA1 b. tincture of iodine; PA1 c. elemental iodine and turpentine; PA1 d. hydrogen peroxide; PA1 e. antimony trichloride or butter of antimony; PA1 f. household bleach (sodium hypochlorite); PA1 g. calomel; PA1 h. creolin; PA1 i. carbolic acid; PA1 j. bichloride of mercury; PA1 k. copper sulphate powder; PA1 l. alum; or PA1 m. a host of topical, proprietary remedies. PA1 a. Formalin/formaldehyde; PA1 b. copper naphthenate; PA1 c. iodophor tincture; PA1 d. copper sulfate; PA1 e. 2-hydroxymethyl-2-nitro-1,3-propanediol; PA1 f. bluestone; PA1 g. a host of other disinfectants.
However, treatment with the above compounds is not equally effective in all horses. Some horses respond poorly to the above compounds. Others do not respond at all. In addition, many of the above compounds are highly toxic or caustic. Currently, treatment of hoof thrush in horses can be "long, difficult and tedious." Rooney, J. R., The Lame Horse, A. S. Barnes & Co. (1977) at p. 143.
3. Hoof Rot
Common techniques for treating hoof rot in sheep, goats and cattle fall into three overlapping areas, similar to those for treating thrush:
The animals generally stand in or walk through a foot bath containing a solution of any of the above-listed disinfectants for treatment. The Sheepman's Production Handbook, supra, at p. 105; The Stockman's Handbook, supra, at p. 379.
However, treatment with any of the above compounds is not equally effective in all animals and some respond poorly to the above compounds. An additional complication in treating hoof rot is that it is so highly contagious that it can rapidly spread to a majority of animals in a flock or herd. In sheep, for example, a severe outbreak of hoof rot can affect up to 75% of a flock at one time. The Sheepman's Production Handbook, supra, at p. 104.
A further complication in treating hoof rot is the problem of reoccurence of the disease. Even when the animal is effectively treated, the disease is likely to reoccur if and when the animal is returned to wet pasture conditions. Wet, muddy, unsanitary conditions provide an excellent environment for the causative organisms, primarily Spherophorus necrophorus. The Sheepman's Production Handbook, supra, at pp. 104-105.
The following U.S. Patents describe other methods for treating or preventing hoof rot: U.S. Pat. No. 3,821,412 describes a method for controlling or preventing hoof rot by treating the ground, such as pen and pastures where the sheep or cattle spend time, with paraformaldehyde; U.S. Pat. No. 3,961,068 describes a method for the treatment of infections in domestic animals that are caused by Sphaerophorus necrophorus particularly, hoof rot in cattle, sheep and goats, by oral administration of ipronidazole (1-methyl-2-isopropyl-5-nitroimidazole) in the animal's feed or drinking water or by parenteral administration of ipronidazole in injections; U.S. Pat. No. 3,984,540 describes a method of treating damaged and/or infected tissue in animals, including hoof rot in cattle and sheep, by administering a therapeutic mixture of antibiotic and catalyst, in which the catalyst is a water solubel alkali metal silicate with magnesium and calcium ions; U.S. Pat. No. 4,061,751 describes a method for treating hoof rot and liver abscesses in ruminant animals by administering a therapeutically effective amount of a 6-substituted, 3-nitroimidazo [1, 2-b]pyridazine compound.